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1.
EMBO J ; 42(12): e112466, 2023 06 15.
Artículo en Inglés | MEDLINE | ID: mdl-37051721

RESUMEN

Axonemal outer dynein arm (ODA) motors generate force for ciliary beating. We analyzed three states of the ODA during the power stroke cycle using in situ cryo-electron tomography, subtomogram averaging, and classification. These states of force generation depict the prepower stroke, postpower stroke, and intermediate state conformations. Comparison of these conformations to published in vitro atomic structures of cytoplasmic dynein, ODA, and the Shulin-ODA complex revealed differences in the orientation and position of the dynein head. Our analysis shows that in the absence of ATP, all dynein linkers interact with the AAA3/AAA4 domains, indicating that interactions with the adjacent microtubule doublet B-tubule direct dynein orientation. For the prepower stroke conformation, there were changes in the tail that is anchored on the A-tubule. We built models starting with available high-resolution structures to generate a best-fitting model structure for the in situ pre- and postpower stroke ODA conformations, thereby showing that ODA in a complex with Shulin adopts a similar conformation as the active prepower stroke ODA in the axoneme.


Asunto(s)
Dineínas , Tomografía con Microscopio Electrónico , Dineínas/metabolismo , Dineínas Axonemales/química , Dineínas Axonemales/metabolismo , Axonema/metabolismo , Cilios/metabolismo , Adenosina Trifosfato , Flagelos/metabolismo
2.
J Liposome Res ; 34(1): 124-134, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37555618

RESUMEN

Liposomes (LPs) are a delivery system for stabilizing pharmaceuticals with limited use due to their propensity to congregate and fuse. A proposed method of addressing these problems is polymer coating. In this study, the potential of octadecylamine (ODA)-coated liposomes and carboxymethyl chitosan (CMCS/ODA-LPs) for enhancing Wacao pentacyclic triterpene saponin (WPTS) transport capacity was investigated. CMCS/ODA-LPs were produced by electrostatic adsorption and thin-film hydration. Response surface methodology (RSM) was employed to enhance the process and encapsulation efficiency (EE) for optimum drug encapsulation efficiency. The synthesized WPTS-CMCS/ODA-LPs were uniformly dispersed in a circular shape, and during 14 days of storage at 4 °C, the particle size and morphology did not significantly change. Vesicle size, zeta potential, polydispersity index (PDI), and entrapment efficiency (%) were 179.1 ± 7.31 nm, -29.6 ± 1.35 mV, 0.188 ± 0.052, and 75.62 ± 0.43, respectively. The hemolysis test revealed that WPTS-CMCS/ODA-LPs were sufficiently biocompatible. Compared to WPTS-LPs, WPTS-CMCS/ODA-LPs consistently showed a much more significant cytotoxic effect on cancer cells. Early and WPTS-CMCS/ODA-LPs-induced apoptosis resulted in almost seven times more cell death than the control. Compared to physiological pH 7.3, the pH-sensitive CMCS coupled LPs increased drug release at acidic pH 6.5. These findings suggest the efficacy of pH-sensitive CMCS/ODA-LPs as a medication delivery method for WPTS.


Asunto(s)
Aminas , Antineoplásicos , Quitosano , Liposomas , Lipopolisacáridos , Tamaño de la Partícula
3.
Genet Med ; 25(5): 100798, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-36727596

RESUMEN

PURPOSE: Primary ciliary dyskinesia (PCD) is a heterogeneous disorder that includes respiratory symptoms, laterality defects, and infertility caused by dysfunction of motile cilia. Most PCD-causing variants result in abnormal outer dynein arms (ODAs), which provide the generative force for respiratory ciliary beating and proper mucociliary clearance. METHODS: In addition to studies in mouse and planaria, clinical exome sequencing and functional analyses in human were performed. RESULTS: In this study, we identified homozygous pathogenic variants in CLXN (EFCAB1/ODAD5) in 3 individuals with laterality defects and respiratory symptoms. Consistently, we found that Clxn is expressed in mice left-right organizer. Transmission electron microscopy depicted ODA defects in distal ciliary axonemes. Immunofluorescence microscopy revealed absence of CLXN from the ciliary axonemes, absence of the ODA components DNAH5, DNAI1, and DNAI2 from the distal axonemes, and mislocalization or absence of DNAH9. In addition, CLXN was undetectable in ciliary axonemes of individuals with defects in the ODA-docking machinery: ODAD1, ODAD2, ODAD3, and ODAD4. Furthermore, SMED-EFCAB1-deficient planaria displayed ciliary dysmotility. CONCLUSION: Our results revealed that pathogenic variants in CLXN cause PCD with defects in the assembly of distal ODAs in the respiratory cilia. CLXN should be referred to as ODA-docking complex-associated protein ODAD5.


Asunto(s)
Cilios , Síndrome de Kartagener , Humanos , Animales , Ratones , Cilios/genética , Síndrome de Kartagener/genética , Síndrome de Kartagener/metabolismo , Síndrome de Kartagener/patología , Proteínas de Unión al Calcio , Axonema/genética , Axonema/metabolismo , Axonema/patología , Mutación , Dineínas Axonemales/genética , Dineínas Axonemales/metabolismo
4.
Bioorg Med Chem ; 80: 117170, 2023 02 15.
Artículo en Inglés | MEDLINE | ID: mdl-36696875

RESUMEN

Many new drugs have been approved over the past decade for rare or orphan diseases. The passage of the Orphan Drug Act (ODA) in 1983 has provided key economic and regulatory incentives to provide medicines for patients who are suffering from rare diseases that may not be commercially attractive for research and development. We have analyzed 497 novel drugs approved from 2010 - June 13, 2022, of which 220 were given orphan designation status. We discuss trends over this time period, potential risks for long development times, and provide example case studies of successful development and launch of novel drugs for rare diseases.


Asunto(s)
Enfermedades Metabólicas , Enfermedades Raras , Estados Unidos , Humanos , Enfermedades Raras/tratamiento farmacológico , Aprobación de Drogas , United States Food and Drug Administration , Producción de Medicamentos sin Interés Comercial
5.
Am J Hum Genet ; 105(1): 198-212, 2019 07 03.
Artículo en Inglés | MEDLINE | ID: mdl-31178125

RESUMEN

Motile cilia and sperm flagella share an evolutionarily conserved axonemal structure. Their structural and/or functional defects are associated with primary ciliary dyskinesia (PCD), a genetic disease characterized by chronic respiratory-tract infections and in which most males are infertile due to asthenozoospermia. Among the well-characterized axonemal protein complexes, the outer dynein arms (ODAs), through ATPase activity of their heavy chains (HCs), play a major role for cilia and flagella beating. However, the contribution of the different HCs (γ-type: DNAH5 and DNAH8 and ß-type: DNAH9, DNAH11, and DNAH17) in ODAs from both organelles is unknown. By analyzing five male individuals who consulted for isolated infertility and displayed a loss of ODAs in their sperm cells but not in their respiratory cells, we identified bi-allelic mutations in DNAH17. The isolated infertility phenotype prompted us to compare the protein composition of ODAs in the sperm and ciliary axonemes from control individuals. We show that DNAH17 and DNAH8, but not DNAH5, DNAH9, or DNAH11, colocalize with α-tubulin along the sperm axoneme, whereas the reverse picture is observed in respiratory cilia, thus explaining the phenotype restricted to sperm cells. We also demonstrate the loss of function associated with DNAH17 mutations in two unrelated individuals by performing immunoblot and immunofluorescence analyses on sperm cells; these analyses indicated the absence of DNAH17 and DNAH8, whereas DNAH2 and DNALI, two inner dynein arm components, were present. Overall, this study demonstrates that mutations in DNAH17 are responsible for isolated male infertility and provides information regarding ODA composition in human spermatozoa.


Asunto(s)
Astenozoospermia/complicaciones , Dineínas Axonemales/genética , Infertilidad Masculina/etiología , Mutación , Espermatozoides/patología , Adulto , Humanos , Infertilidad Masculina/metabolismo , Infertilidad Masculina/patología , Masculino , Linaje , Fenotipo , Espermatozoides/metabolismo
6.
BMC Public Health ; 21(1): 2175, 2021 11 27.
Artículo en Inglés | MEDLINE | ID: mdl-34837970

RESUMEN

BACKGROUND: Japan strives to strengthen its development cooperation by mobilizing various resources to assist partner countries advance on Universal Health Coverage by 2030. However, the involvement and roles of various actors for health are not clear. This study is the first to map Japan's publicly funded projects by both Official Development Assistance (ODA) and other non-ODA public funds, and to describe the intervention areas. Further, the policy implications for country-specific cooperation strategies are discussed. The development cooperation for health in Vietnam is used as a case in this study. METHODS: A cross-sectional analysis of the Japanese publicly funded health projects that were being implemented in Vietnam during December 2016 was conducted. A framework of analysis based on the World Health Organization six health systems building blocks was adopted. The projects' qualitative information was also assessed. RESULTS: Overall, 68 projects implemented through Japanese public funding were analyzed. These 68 projects under 15 types of schemes were managed by seven different scheme-operating organizations and funded by five ministries. Of these 44 (64.7%) were ODA and 24 (35.3%) were non-ODA projects. Among the recategorized six building blocks of the health system, the largest proportion of projects was health service delivery (44%), followed by health workforces (25%), and health information systems (15%). Almost half the projects were implemented together with the central hospitals as Vietnamese counterparts, which suggests that this is one area in which the specificities of Japanese cooperation are demonstrated. No synergetic effects of potential collaboration or harmonization among Japanese funded projects were captured. CONCLUSIONS: Several Japanese-funded projects addressed a wide range of health issues across all six building blocks of the health system in Vietnam. However, there is room for improvement in developing coordination and harmonization among the diversified Japanese projects. Establishing a country-specific mechanism for strategic coordination across Japanese ministries' schemes can yield efficient and effective development cooperation for health. While Vietnam's dependence on external funding is low, the importance of coordination across domestic actors of the donor countries can serve as an important lesson, especially in beneficiary countries with high external funding dependency.


Asunto(s)
Cooperación Internacional , Estudios Transversales , Humanos , Japón , Vietnam , Organización Mundial de la Salud
7.
Molecules ; 26(12)2021 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-34204264

RESUMEN

The present research investigated the chemical characterization and insecticidal activity of n-Hexane extracts of Epaltes divaricata (NH-EDx) along with their chief derivatives n-Hexadecanoic acid (n-HDa) and n-Octadecanoic acid (n-ODa) against the dengue vector Aedes aegypti and lepidopteran pest Spodoptera litura. Chemical screening of NH-EDx through GC-MS analysis delivered nine major derivatives, and the maximum peak area percentage was observed in n-Hexadecanoic acid (14.63%) followed by n-Octadecadienoic acid (6.73%). The larvicidal activity of NH-EDx (1000 ppm), n-HDa (5 ppm), and n-ODa (5 ppm) against the A. aegypti and S. litura larvae showed significant mortality rate in a dose-dependent way across all the instars. The larvicidal activity was profound in the A. aegypti as compared to the S. litura across all the larval instars. The sublethal dosages of NH-EDx (500 ppm), n-HDa (2.5 ppm), and n-ODa (2.5 ppm) also showed alterations in the larval/pupal durations and adult longevity in both the insect pests. The enzyme activity revealed that the α- and ß-carboxylesterase levels were decreased significantly in both the insect pests, whereas the levels of GST and CYP450 uplifted in a dose-dependent manner of NH-EDx, n-HDa, and n-ODa. Correspondingly, midgut tissues such as the epithelial layer (EL), gut lumen (GL), peritrophic matrix (Pm), and brush border membrane (BBM) were significantly altered in their morphology across both A. aegypti and S. litura against the NH-EDx and their bioactive metabolites. NH-EDx and their bioactive metabolites n-HDa and n-ODa showed significant larvicidal, growth retardant, enzyme inhibition, and midgut toxicity effects against two crucial agriculturally and medically challenging insect pest of ecological importance.


Asunto(s)
Aedes/efectos de los fármacos , Asteraceae/metabolismo , Extractos Vegetales/farmacología , Spodoptera/efectos de los fármacos , Animales , Asteraceae/efectos de los fármacos , Culex/efectos de los fármacos , Dengue/prevención & control , Hexanos/química , Insecticidas/farmacología , Larva/efectos de los fármacos , Mosquitos Vectores/efectos de los fármacos , Hojas de la Planta/química , Solventes/química
8.
World Dev ; 135: 105059, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-32834375

RESUMEN

The COVID-19 pandemic is increasing the need for international food assistance, and disrupting the supply and delivery of food assistance. A series of unprecedented shocks is straining the capacity of food assistance organizations to reach vulnerable populations. We discuss how the COVID-19 pandemic is affecting the demand and the supply of international food assistance, and we propose three policy changes that can keep food flowing to those in need. First, donor countries can prioritize humanitarian spending in aid-allocation decisions. Second, governments can exempt food assistance from trade barriers that impede procurement (export restrictions) and delivery (import tariffs). Third, donor countries can allow flexibility for implementing agencies by untying food assistance from domestic procurement and shipping restrictions. All of these proposals are regulatory changes that can be made without requiring increased spending. These options are particularly relevant now because donor-country governments are entering economic recessions, and foreign aid budgets will be constrained.

9.
Global Health ; 15(1): 66, 2019 11 21.
Artículo en Inglés | MEDLINE | ID: mdl-31752921

RESUMEN

BACKGROUND: In 2018, the Australian Government, through a Senate-led Parliamentary Inquiry, sought the views of diverse stakeholders on Sustainable Development Goal (SDG) implementation both domestically and as part of Australia's Overseas Development Assistance (ODA) program. One hundred and sixty-four written submissions were received. The submissions offered perspective and guidance from a rich cross-section of those involved, and with keen interest in, Australia's ODA-SDG commitment. This article identifies and explores the submissions to that Inquiry which placed impetus on Australia's ODA-SDG and health and development nexus. It then compares how the synthesized views, concerns and priorities of selected Inquiry stakeholders align with and reflect the Australian Government's treatment of SDG 3 in its SDG Voluntary National Review (VNR), as well as with the final Inquiry report summarizing submission content. RESULTS: Four key themes were synthesized and drawn from the thirty-one stakeholder submissions included in our analysis. Disconnect was then found to exist between the selected stakeholder views and the Australian Government's SDG-VNR's treatment of SDG 3, as well as with the content of the Parliamentary Inquiry's final report with respect to the ODA-SDG and health and development nexus. CONCLUSIONS: We situate the findings of our analysis within the wider strategic context of the Australian Government's policy commitment to "step up" in the Pacific region. This research provides an insight into both multi-stakeholder and Federal Government views on ODA in the Indo-Pacific region, especially at a time when Australia's Pacific engagement has come to the forefront of both foreign and security policy. We conclude that the SDG agenda, including the SDG health and development agenda, could offer a unique vehicle for enabling a paradigm shift in the Australian Government's development approach toward the Pacific region and its diverse peoples. This potential is strongly reflected in stakeholder perspectives included in our analysis. However, study findings remind that the political determinants of health, and overlapping political determinants of SDG achievement, will be instrumental in the coming decade, and that stakeholders from different sectors need to be genuinely engaged in SDG-ODA policy-related decision-making and planning by governments in both developed and developing countries alike.


Asunto(s)
Salud Global/economía , Cooperación Internacional , Desarrollo Sostenible/economía , Australia , Gobierno , Humanos , Participación de los Interesados
10.
Int J Mol Sci ; 20(24)2019 Dec 07.
Artículo en Inglés | MEDLINE | ID: mdl-31817850

RESUMEN

The outer and inner dynein arms (ODAs and IDAs) are composed of multiple subunits including dynein heavy chains possessing a motor domain. These complex structures are preassembled in the cytoplasm before being transported to the cilia. The molecular mechanism(s) controlling dynein arms' preassembly is poorly understood. Recent evidence suggests that canonical R2TP complex, an Hsp-90 co-chaperone, in cooperation with dynein axonemal assembly factors (DNAAFs), plays a crucial role in the preassembly of ODAs and IDAs. Here, we have summarized recent data concerning the identification of novel chaperone complexes and their role in dynein arms' preassembly and their association with primary cilia dyskinesia (PCD), a human genetic disorder.


Asunto(s)
Axonema/metabolismo , Cilios/fisiología , Dineínas/metabolismo , Proteínas HSP90 de Choque Térmico/metabolismo , Chaperonas Moleculares/metabolismo , Animales , Humanos
11.
Adv Exp Med Biol ; 1031: 183-196, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-29214572

RESUMEN

Over 30 years ago, the United States (US) Congress passed the Orphan Drug Act (ODA) to encourage the development of products for rare diseases or conditions ("orphan products"). The Act provided incentives to sponsors for developing products with orphan designation and established a grant program to fund studies of orphan products. Since its enactment in 1983, the ODA has been credited for bringing more than 590 orphan drugs to the market, inspiring the implementation of orphan legislation globally, and enabling the creation of other programs that extend existing knowledge of the natural history of rare diseases and stimulate the development of medical devices for children and patients with rare diseases. This chapter provides a brief overview of the main features and successes of 5 of the orphan incentive programs administered by the US Food and Drug Administration (FDA): the Orphan Drug Designation Program, the Humanitarian Use Device (HUD) Designation Program, the Orphan Products Clinical Trials Grants Program, the Pediatric Device Consortia (PDC) Grant Program, and the Orphan Products Natural History Grants Program.


Asunto(s)
Aprobación de Drogas , Descubrimiento de Drogas/métodos , Industria Farmacéutica , Motivación , Producción de Medicamentos sin Interés Comercial , Enfermedades Raras/tratamiento farmacológico , United States Food and Drug Administration , Aprobación de Drogas/legislación & jurisprudencia , Descubrimiento de Drogas/legislación & jurisprudencia , Industria Farmacéutica/legislación & jurisprudencia , Regulación Gubernamental , Humanos , Producción de Medicamentos sin Interés Comercial/legislación & jurisprudencia , Desarrollo de Programa , Evaluación de Programas y Proyectos de Salud , Enfermedades Raras/diagnóstico , Enfermedades Raras/epidemiología , Estados Unidos , United States Food and Drug Administration/legislación & jurisprudencia
12.
BJOG ; 123(10): 1693-704, 2016 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-26817807

RESUMEN

OBJECTIVE: To provide information on trends on official development assistance (ODA) disbursement patterns for reproductive health activities in 18 conflict-affected countries. DESIGN: Secondary data analysis. SAMPLE: 18 conflict-affected countries and 36 non-conflict-affected countries. METHODS: The Creditor Reporting System (CRS) database was analyzed for ODA disbursement for direct and indirect reproductive health activities to 18 conflict-affected countries (2002-2011). A comparative analysis was also made with 36 non-conflict-affected counties in the same 'least-developed' income category. Multivariate regression analyses examined associations between conflict status and reproductive health ODA and between reproductive needs and ODA disbursements. MAIN OUTCOME MEASURES: Patterns of ODA disbursements (constant U.S. dollars) for reproductive health activities. RESULTS: The average annual ODA disbursed for reproductive health to 18 conflict-affected countries from 2002 to 2011 was US$ 1.93 per person per year. There was an increase of 298% in ODA for reproductive health activities to the conflict-affected countries between 2002 and 2011; 56% of this increase was due to increases in HIV/AIDS funding. The average annual per capita reproductive health ODA disbursed to least-developed non-conflict-affected countries was 57% higher than to least-developed conflict-affected countries. Regression analyses confirmed disparities in ODA to and between conflict-affected countries. CONCLUSIONS: Despite increases in ODA for reproductive health for conflict-affected countries (albeit largely for HIV/AIDS activities), considerable disparities remains. TWEETABLE ABSTRACT: Study tracking 10 years of aid for reproductive aid shows major disparities for conflict-affected countries.


Asunto(s)
Conflictos Armados , Apoyo Financiero , Cooperación Internacional , Salud Reproductiva/economía , Guerra , Países en Desarrollo/economía , Femenino , Fundaciones , Salud Global , Disparidades en Atención de Salud , Financiación de la Atención de la Salud , Humanos
13.
J Colloid Interface Sci ; 669: 327-335, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38718586

RESUMEN

Nanobubbles (NBs) are classified in two distinct categories: surface and bulk. Surface NBs are readily observed using atomic force microscopy (AFM), while the existence of bulk NBs has been a subject of debate, conflicting with the diffusion theory's predictions. Current methodologies for identifying bulk NBs yield inconclusive results. In this study, Langmuir Blodgett (LB) technique and AFM, are utilized to visualize NB imprints on anionic, cationic and zwitterionic lipid films deposited on glass-slide substrates. Our analysis of Langmuir monolayers compression isotherms reveals the impact of bulk NBs on lipid monolayer development. AFM scans of the deposited lipid films consistently show NB imprints. Notably, cationic and zwitterionic film depositions exhibit NB formations from the 1st layer, whereas in anionic films, these formations are observed only after the 3rd layer. These results suggest that the origin of these imprinted formations may be attributed to bulk NBs.

14.
J Struct Biol ; 183(3): 305-311, 2013 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-23859837

RESUMEN

There are a number of large macromolecular complexes that play important roles in the cell, and identifying the positions of their components is a key step to understanding their structure and function. Several structural labeling methods have been applied to electron microscopy in order to locate a specific component within a macromolecular complex, but each method is associated with problems in specificity, occupancy, signal intensity or precision. Here, we report a novel method for identifying the 3D locations of proteins using biotin-streptavidin labeling and cryo-electron tomography. We labeled a biotinylation-tagged intermediate chain of an axonemal dynein by streptavidin within the Chlamydomonas axoneme and visualized the 3D positions of the labels using subtomogram averaging. Increase of the density attributed to the bound streptavidin was validated by Student's t-test. In conclusion, the combination of the biotin-streptavidin system and cryo-electron tomography is a powerful method to investigate the structure of large macromolecular complexes.


Asunto(s)
Axonema/ultraestructura , Biotina/química , Chlamydomonas reinhardtii/ultraestructura , Proteínas de Plantas/metabolismo , Estreptavidina/química , Secuencia de Aminoácidos , Axonema/química , Biotina/biosíntesis , Microscopía por Crioelectrón , Tomografía con Microscopio Electrónico , Imagenología Tridimensional , Conformación Molecular , Datos de Secuencia Molecular , Proteínas de Plantas/química , Unión Proteica , Coloración y Etiquetado/métodos
15.
Biochem Biophys Res Commun ; 440(2): 204-9, 2013 Oct 18.
Artículo en Inglés | MEDLINE | ID: mdl-24025677

RESUMEN

6-Octadecynoic acid (6-ODA), a fatty acid with a triple bond, was identified in the methanol extract of Marrubium vulgare L. as an agonist of peroxisome proliferator-activated receptor γ (PPARγ). Fibrogenesis caused by hepatic stellate cells is inhibited by PPARγ whose ligands are clinically used for the treatment of diabetes. Plant extracts of Marrubium vulgare L., were screened for activity to inhibit fibrosis in the hepatic stellate cell line HSC-T6 using Oil Red-O staining, which detects lipids that typically accumulate in quiescent hepatic stellate cells. A methanol extract with activity to stimulate accumulation of lipids was obtained. This extract was found to have PPARγ agonist activity using a luciferase reporter assay. After purification using several chromatographic methods, 6-ODA, a fatty acid with a triple bond, was identified as a candidate of PPARγ agonist. Synthesized 6-ODA and its derivative 9-octadecynoic acid (9-ODA), which both have a triple bond but in different positions, activated PPARγ in a luciferase reporter assay and increased lipid accumulation in 3T3-L1 adipocytes in a PPARγ-dependent manner. There is little information about the biological activity of fatty acids with a triple bond, and to our knowledge, this is the first report that 6-ODA and 9-ODA function as PPARγ agonists.


Asunto(s)
Ácidos Grasos Monoinsaturados/farmacología , Células Estrelladas Hepáticas/efectos de los fármacos , PPAR gamma/agonistas , Extractos Vegetales/farmacología , Células 3T3-L1 , Alquinos/farmacología , Animales , Ácidos Grasos Insaturados/farmacología , Humanos , Marrubium/química , Ratones
16.
Mol Genet Metab ; 109(4): 319-28, 2013 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-23806236

RESUMEN

A trans-National Institutes of Health initiative, Nutrition and Dietary Supplement Interventions for Inborn Errors of Metabolism (NDSI-IEM), was launched in 2010 to identify gaps in knowledge regarding the safety and utility of nutritional interventions for the management of inborn errors of metabolism (IEM) that need to be filled with evidence-based research. IEM include inherited biochemical disorders in which specific enzyme defects interfere with the normal metabolism of exogenous (dietary) or endogenous protein, carbohydrate, or fat. For some of these IEM, effective management depends primarily on nutritional interventions. Further research is needed to demonstrate the impact of nutritional interventions on individual health outcomes and on the psychosocial issues identified by patients and their families. A series of meetings and discussions were convened to explore the current United States' funding and regulatory infrastructure and the challenges to the conduct of research for nutritional interventions for the management of IEM. Although the research and regulatory infrastructure are well-established, a collaborative pathway that includes the professional and advocacy rare disease community and federal regulatory and research agencies will be needed to overcome current barriers.


Asunto(s)
Dieta , Errores Innatos del Metabolismo/dietoterapia , Fenómenos Fisiológicos de la Nutrición , Suplementos Dietéticos , Manejo de la Enfermedad , Vías de Administración de Medicamentos , Humanos , Errores Innatos del Metabolismo/genética , Enfermedades Raras , Estados Unidos
17.
Glob Health Action ; 16(1): 2258707, 2023 12 31.
Artículo en Inglés | MEDLINE | ID: mdl-37733029

RESUMEN

BACKGROUND: Official Development Assistance (ODA) significantly aids sustainable development in low- and middle-income countries (LMICs). However, the COVID-19 pandemic has impacted aid allocation, posing challenges for attaining the Sustainable Development Goals (SDGs). OBJECTIVE: This study explores and underscores the profound implications of shifts in ODA allocation by Development Assistance Committee (DAC) member countries, resulting from the COVID-19 pandemic, offering a unique perspective on the evolving landscape of international aid. METHODS: Drawing from the gross ODA disbursement data for LMICs by DAC member countries from 2011 to 2021, a linear regression analysis assessed the changes in ODA amount, ODA-to-gross national income (GNI) ratio, sectoral aid allocation, and the balance between bilateral and multilateral aid, primarily focusing on the differences pre- and post-COVID-19. For non-specialised multilateral agencies' core funding, the OECD's methodology for calculating imputed multilateral ODA was employed to estimate ODA flows. RESULTS: The study found an increasing trend in the total ODA provided by DAC member countries from 2011 to 2021. However, the average ODA/GNI ratio showed a slight but significant decrease before the pandemic, followed by an increase after the COVID-19 pandemic. The health sector received the highest percentage of aid after the pandemic, with a marked increase in both bilateral and multilateral aid. However, other sectors such as humanitarian aid, water and sanitation, and energy experienced a significant decrease in sectoral aid share. CONCLUSIONS: Emerging from this analysis is a strong recommendation for DAC members to re-evaluate aid objectives and escalate their financial commitments to reinforce SDGs and sustainable development efforts. While the rise in health aid is essential, other sectors also require equal focus to offset the ramifications of the COVID-19 pandemic. Understanding the intricacies of aid allocation can improve aid efficacy, culminating in greater, transformative results for recipient countries.


Asunto(s)
COVID-19 , Humanos , COVID-19/epidemiología , Pandemias , Renta , Saneamiento
18.
Eur J Dev Res ; 34(2): 611-654, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-33716409

RESUMEN

International efforts have taken place to alleviate poverty by adopting several obligations within the international society; one of these obligations is the provision of safe access to water and sanitation. The MDGs helped people around the world to gain improved water sources and better sanitation. Although the sectoral aid increased from 20% between 1990 and 1992 (only 4.9% distributed for water supply and sanitation (W&S)) to 35% between 2002 and 2004 (only 3.9% allocated for W&S), facts showed that the allocated aid was biased to social aims rather than infrastructural targets. In this study, I am focusing on the donors' commitment for W&S, whether their ODA for these two sub-sectors is aligned with the intentions of the SDGs. I find that donors allocated W&S aid by focusing on governments in general with higher governance indicators, and that poorer countries received a higher allocation of aid.


Les efforts internationaux pour la réduction de la pauvreté ont pris forme à travers de plusieurs obligations adoptés par la société internationale. Une de ces obligations est l'approvisionnement d'accès sécuritaire à l'eau et à l'assainissement (en anglais, water supply and sanitation, W&S). Les Objectifs du Millénaire pour le Développement (en anglais : Millenuim Development Goals, MDGs) ont aidé des gens partout dans le monde à bénéficier d'un meilleur approvisionnement d'eau, et d'accès a des installations sanitaires. Même si l'aide dédié e ce secteur a augmenté du 20% en 1990-1992 (que 4.9% distribué pour W&S) au 35% en 2002-2004 (que 3.9% dédié à W&S), les faits nous démontrent que cet aide est biaisé vers des finalités sociales plutôt que des objectifs d'infrastructure. Dans cet étude, nous nous focalisons sur l'engagement des donneurs envers W&S, pour voir si leur aide officielle au développement (en anglais : Official Development Assistance, ODA) pour ces deux secteurs est aligné avec les intentions des objectifs de développement durable (en anglais : Sustainable Development Goals, SDGs). Nous trouvons que les donneurs affectent leur aide W&S se focalisant généralement sur les gouvernements avec des meilleurs indicateurs de gouvernance, et que les pays les plus pauvres reçoivent une affectation d'aide supérieure.

19.
J Migr Health ; 5: 100090, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35373164

RESUMEN

Background: There are an estimated 55 million internally displaced persons (IDPs) globally. IDPs commonly have worse health outcomes than host populations and other forcibly displaced populations such as refugees. Official development assistance (ODA) is a major source of the global financial response for health in low- and middle-income countries (LMICs), including for populations affected by armed conflict and forced displacement. Analysis of ODA supports efforts to improve donor accountability, transparency and the equitable use of ODA. The aim of this study is to examine international donor support and responsiveness to IDP health needs through analysis of ODA disbursements to LMICs between 2010 and 2019. Methods: ODA disbursement data to LMICs from 2010 to 2019 were extracted from the Creditor Reporting System (CRS) database and analysed with Stata software using a combination of: (i) text searching for IDP and refugee related terms; and (ii) relevant health and humanitarian CRS purpose codes. Descriptive analysis was used to examine patterns of ODA disbursement, and nonlinear least squared regression analysis was used to examine responsiveness of ODA disbursement to recipient country IDP population size and health system capacity and health characteristics. Findings: The study highlighted declining per IDP capita health ODA from USD 5.34 in 2010 to USD 3.72 in 2019 (with annual average decline of -38% from the 2010 baseline). In contrast, health ODA for refugees in LMICs increased from USD 18.55 in 2010 to USD 23.31 in 2019 (with an annual average increase of +14%). Certain health topics for IDPs received very low ODA, with only 0.44% of IDP health ODA disbursed for non-communicable diseases (including mental health). There was also weak evidence of IDP health ODA being related to recipient country IDP population size, and health system capacity and health characteristics. The paper highlights the need for increased investment by donors in IDP health ODA and to ensure that it is responsive to their health needs.

20.
Environ Sci Pollut Res Int ; 28(41): 57952-57969, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34105072

RESUMEN

The suitable temperature of circulating cooling water is conducive to the reproduction of bacteria, which will cause corrosion to the pipe and form slime on its surface. Therefore, the sterilization of circulating cooling water is an essential step. In this work, a new type of SA-CuZnO@ODA-GO composite antibacterial material with hydrophobic properties was prepared by ultrasonic treatment method. The composite was characterized and analyzed by SEM, TEM, XPS, XRD, and FT-IR. Then, the CuZnO@ODA-GO@PU hydrophobic and antibacterial coating was prepared. The antibacterial properties and mechanism of the composite were investigated by gram-positive bacteria S. aureus and gram-negative bacteria E. coli. The result shows that the best antibacterial rate of SA-CuZnO@ODA-GO composite antibacterial material is up to 99.10%. As for the SA-CuZnO@ODA-GO@PU composite antibacterial coating, the corrosion resistance of the antibacterial coating is up to 99.99%. The anticorrosion property is due to the hydrophobic modification of the composite, which can insulate the steel sheet from water. Secondly, due to the rigidity of the SA-CuZnO@ODA-GO, it combines with epoxy resin to form a compact structure.


Asunto(s)
Escherichia coli , Staphylococcus aureus , Antibacterianos/farmacología , Corrosión , Espectroscopía Infrarroja por Transformada de Fourier , Agua
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